- Category: Experimental HCV Drugs
- Published on Wednesday, 16 April 2014 00:00
- Written by Keith Alcorn
A combination of two direct-acting antivirals developed by AbbVie cured 100% of previously untreated patients with hepatitis C genotype 4 infection when used with ribavirin, as well as all treatment-experienced patients followed for 4 weeks post-treatment, Christophe Hézode of Hôpital Henri Mondor in Paris reported at the 49th EASL International Liver Congress last week in London.
Genotype 4 hepatitis C virus (HCV) is the predominant form in Egypt, Nigeria, Cameroon, and Gabon. Genotype 4 accounts for approximately 20% of HCV infections worldwide and is becoming a common genotype among people newly diagnosed with hepatitis C in France, Tarik Asselah of Hôpital Beaujon in Paris told a conference satellite meeting organized by AbbVie. Between 7% and 20% of HCV infections in France, Italy, and Spain are genotype 4, due in part to migration within the Mediterranean region and from sub-Saharan Africa.
Genotype 4 HCV has been considered hard to treat compared to genotypes 2 and 3. Not all direct-acting antivirals are active against genotype 4, or else they have been tested in very small populations.
The PEARL-I study examined the safety and efficacy of the protease inhibitor ABT-450 with ritonavir booster (150/100 mg once-daily), in combination with the NS5A inhibitor ombitasvir (ABT-267; 250 mg once-daily), with or without ribavirin. (AbbVie is also developing these agents as part of a 3-drug combination that also includes the non-nucleoside NS5B polymerase inhibitor dasabuvir [ABT-333), which is not active against genotype 4.)
The study population comprised previously untreated and treatment-experienced people with HCV genotype 4, who did not have cirrhosis.
All study participants received treatment with ABT-450/ritonavir and ombitasvir for 12 weeks. People who had not taken treatment before were randomized to receive therapy without (n=44) or with (n=42) ribavirin. The treatment-experienced patients all received ribavirin.
Most participants were white (84%-92% by arm) and male (55%-74%). Between 67% and 86% and had fibrosis stage F0 or F1 while about one-quarter had moderate or advanced liver fibrosis (stage F2-F3). In the treatment-experienced arm, 35% had relapsed on a previous regimen of pegylated interferon and ribavirin, 18% had shown a partial response, and 47% had shown null response. Mean HCV viral load at baseline was approximately 6.1 log IU/ml.
All 42 treatment-naive patients in the ribavirin-containing arm achieved SVR12, or continued undetectable HCV RNA 12 weeks after finishing treatment. The SVR12 rate was 91% in the ribavirin-sparing arm: 1 patient was lost to follow up, 1 patient experienced viral breakthrough before completion of treatment, and 2 patients experienced viral relapse after completing treatment and prior to the week-12 post-treatment follow-up visit.
All 49 treatment-experienced participants had an end-of-treatment virological response and SVR4 results were presented for 37 treatment-experienced patients who reached the 4-week post-treatment follow-up visit, all of whom still had undetectable virus. SVR12 results will be required in order to determine if all patients have achieved a cure.
No patient stopped treatment due to side effects and the only serious adverse event occurred as a result of a car accident unrelated to treatment. The most common side effects were fatigue and headache. 3 patients in the treatment-experienced arm had transient elevations in bilirubin, and 4 patients experienced hemoglobin declines (including 1 in the ribavirin-sparing arm). None required ribavirin dose reduction.
"All-oral, interferon-free, 12-week regimens of ABT-450/ritonavir + ombitasvir resulted in high SVR12 rates in treatment-naive HCV genotype 4-infected patients ...[and] an SVR4 rate of 100% in treatment-experienced patients receiving ABT-450/ritonavir + ombitasvir + ribavirin," concluded the researchers.
C Hezode, P Marcellin, S Pol, et al. Results from the phase 2 PEARL-I study: interferon-free regimens of ABT-450/R + ABT-267 with or without ribavirin in patients with HCV genotype 4 infection. 49th European Association for the Study of the Liver International Liver Congress (EASL 2014). London, April 9-13, 2014. Abstract O58.
AbbVie. AbbVie to Present Late-Breaking Results from TURQUOISE-II Study in Chronic Hepatitis C Patients with Cirrhosis at the 2014 International Liver Congress. Press release. April 12, 2014.
AbbVie. AbbVie to Present Detailed Results from Phase III Studies in Patients with Chronic Hepatitis C at the 2014 International Liver Congress. Press release. March 24, 2014.
European Association for the Study of the Liver. New Interferon-Free, All-Oral 3D Treatment Regimen Achieves High Rates of Virological Response in Patients Chronically Infected with HCV Genotype 1. Press release. April 12, 2014.